title: Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model.
abstract: BACKGROUND
  Cartilaginous metaplasia of vascular smooth muscle (VSM) is characteristic for arterial calcification in diabetes and uremia and in the background of genetic alterations in matrix Gla protein (MGP). A better understanding of the molecular details of this process is critical for the development of novel therapeutic approaches to VSM transformation and arterial calcification.
  
  
  OBJECTIVE
  This study aimed to identify the effects of bioflavonoid quercetin on chondrogenic transformation and calcification of VSM in the MGP-null mouse model and upon TGF-β3 stimulation in vitro, and to characterize the associated alterations in cell signaling.
  
  
  RESULTS
  Molecular analysis revealed activation of β-catenin signaling in cartilaginous metaplasia in Mgp-/- aortae in vivo and during chondrogenic transformation of VSMCs in vitro. Quercetin intercepted chondrogenic transformation of VSM and blocked activation of β-catenin both in vivo and in vitro. Although dietary quercetin drastically attenuated calcifying cartilaginous metaplasia in Mgp-/- animals, approximately one-half of total vascular calcium mineral remained as depositions along elastic lamellae.
  
  
  CONCLUSIONS
  Quercetin is potent in preventing VSM chondrogenic transformation caused by diverse stimuli. Combined with the demonstrated efficiency of dietary quercetin in preventing ectopic chondrogenesis in the MGP-null vasculature, these findings indicate a potentially broad therapeutic applicability of this safe for human consumption bioflavonoid in the therapy of cardiovascular conditions linked to cartilaginous metaplasia of VSM. Elastocalcinosis is a major component of MGP-null vascular disease and is controlled by a mechanism different from chondrogenic transformation of VSM and not sensitive to quercetin.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Beazley
authors.forename: Florence
authors.initials: F
authors.lastname: Lima
authors.forename: Teresa
authors.initials: T
authors.lastname: Borras
authors.forename: Maria
authors.initials: M
authors.lastname: Nurminskaya
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D020219:Chondrogenesis / Q000187:drug effects*; D017931:DNA Primers / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D007150:Immunohistochemistry; D008156:Luciferases; D008679:Metaplasia / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*; D011794:Quercetin / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D061205:Vascular Calcification / Q000188:drug therapy* / Q000503:physiopathology; D051176:beta Catenin / Q000378:metabolism; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D008156:Luciferases; D011794:Quercetin; D051176:beta Catenin; D000097568:Matrix Gla Protein